Serveur d'exploration sur la glutarédoxine

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Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1).

Identifieur interne : 000418 ( Main/Exploration ); précédent : 000417; suivant : 000419

Salvianolic Acid B (Sal B) Protects Retinal Pigment Epithelial Cells from Oxidative Stress-Induced Cell Death by Activating Glutaredoxin 1 (Grx1).

Auteurs : Xiaobin Liu [États-Unis] ; Christy Xavier [États-Unis] ; Jamieson Jann [États-Unis] ; Hongli Wu [États-Unis]

Source :

RBID : pubmed:27827892

Descripteurs français

English descriptors

Abstract

Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG) between cysteine residues and glutathione (GSH), can lead to cell death. Glutaredoxin 1 (Grx1) is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B), a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE) cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H₂O₂-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2), the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of Grx1 by small interfering RNA (siRNA) significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H₂O₂-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage.

DOI: 10.3390/ijms17111835
PubMed: 27827892
PubMed Central: PMC5133836


Affiliations:


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Le document en format XML

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<term>Benzofurans (pharmacology)</term>
<term>Disulfides (metabolism)</term>
<term>Dose-Response Relationship, Drug (MeSH)</term>
<term>Drugs, Chinese Herbal (pharmacology)</term>
<term>Enzyme Activation (drug effects)</term>
<term>Epithelial Cells (cytology)</term>
<term>Epithelial Cells (drug effects)</term>
<term>Epithelial Cells (metabolism)</term>
<term>Fetus (MeSH)</term>
<term>Gene Expression Regulation (MeSH)</term>
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<term>Glutaredoxins (genetics)</term>
<term>Glutaredoxins (metabolism)</term>
<term>Glutathione (metabolism)</term>
<term>Humans (MeSH)</term>
<term>Hydrogen Peroxide (antagonists & inhibitors)</term>
<term>Hydrogen Peroxide (pharmacology)</term>
<term>NF-E2-Related Factor 2 (agonists)</term>
<term>NF-E2-Related Factor 2 (genetics)</term>
<term>NF-E2-Related Factor 2 (metabolism)</term>
<term>Oxidation-Reduction (MeSH)</term>
<term>Oxidative Stress (MeSH)</term>
<term>Primary Cell Culture (MeSH)</term>
<term>RNA, Small Interfering (genetics)</term>
<term>RNA, Small Interfering (metabolism)</term>
<term>Retinal Pigment Epithelium (cytology)</term>
<term>Retinal Pigment Epithelium (drug effects)</term>
<term>Retinal Pigment Epithelium (metabolism)</term>
<term>Signal Transduction (MeSH)</term>
<term>Time Factors (MeSH)</term>
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<term>Activation enzymatique (effets des médicaments et des substances chimiques)</term>
<term>Antioxydants (pharmacologie)</term>
<term>Benzofuranes (pharmacologie)</term>
<term>Cellules épithéliales (cytologie)</term>
<term>Cellules épithéliales (effets des médicaments et des substances chimiques)</term>
<term>Cellules épithéliales (métabolisme)</term>
<term>Culture de cellules primaires (MeSH)</term>
<term>Disulfures (métabolisme)</term>
<term>Facteur-2 apparenté à NF-E2 (agonistes)</term>
<term>Facteur-2 apparenté à NF-E2 (génétique)</term>
<term>Facteur-2 apparenté à NF-E2 (métabolisme)</term>
<term>Facteurs temps (MeSH)</term>
<term>Foetus (MeSH)</term>
<term>Glutarédoxines (antagonistes et inhibiteurs)</term>
<term>Glutarédoxines (génétique)</term>
<term>Glutarédoxines (métabolisme)</term>
<term>Glutathion (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Médicaments issus de plantes chinoises (pharmacologie)</term>
<term>Oxydoréduction (MeSH)</term>
<term>Peroxyde d'hydrogène (antagonistes et inhibiteurs)</term>
<term>Peroxyde d'hydrogène (pharmacologie)</term>
<term>Petit ARN interférent (génétique)</term>
<term>Petit ARN interférent (métabolisme)</term>
<term>Relation dose-effet des médicaments (MeSH)</term>
<term>Régulation de l'expression des gènes (MeSH)</term>
<term>Stress oxydatif (MeSH)</term>
<term>Transduction du signal (MeSH)</term>
<term>Épithélium pigmentaire de la rétine (cytologie)</term>
<term>Épithélium pigmentaire de la rétine (effets des médicaments et des substances chimiques)</term>
<term>Épithélium pigmentaire de la rétine (métabolisme)</term>
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<term>Hydrogen Peroxide</term>
</keywords>
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<term>Glutaredoxins</term>
<term>NF-E2-Related Factor 2</term>
<term>RNA, Small Interfering</term>
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<term>Glutaredoxins</term>
<term>Glutathione</term>
<term>NF-E2-Related Factor 2</term>
<term>RNA, Small Interfering</term>
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<term>Benzofurans</term>
<term>Drugs, Chinese Herbal</term>
<term>Hydrogen Peroxide</term>
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<term>Facteur-2 apparenté à NF-E2</term>
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<term>Glutarédoxines</term>
<term>Peroxyde d'hydrogène</term>
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<term>Épithélium pigmentaire de la rétine</term>
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<term>Retinal Pigment Epithelium</term>
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<term>Activation enzymatique</term>
<term>Cellules épithéliales</term>
<term>Épithélium pigmentaire de la rétine</term>
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<term>Facteur-2 apparenté à NF-E2</term>
<term>Glutarédoxines</term>
<term>Petit ARN interférent</term>
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<term>Epithelial Cells</term>
<term>Retinal Pigment Epithelium</term>
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<term>Cellules épithéliales</term>
<term>Disulfures</term>
<term>Facteur-2 apparenté à NF-E2</term>
<term>Glutarédoxines</term>
<term>Glutathion</term>
<term>Petit ARN interférent</term>
<term>Épithélium pigmentaire de la rétine</term>
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<term>Antioxydants</term>
<term>Benzofuranes</term>
<term>Médicaments issus de plantes chinoises</term>
<term>Peroxyde d'hydrogène</term>
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<term>Dose-Response Relationship, Drug</term>
<term>Fetus</term>
<term>Gene Expression Regulation</term>
<term>Humans</term>
<term>Oxidation-Reduction</term>
<term>Oxidative Stress</term>
<term>Primary Cell Culture</term>
<term>Signal Transduction</term>
<term>Time Factors</term>
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<term>Culture de cellules primaires</term>
<term>Facteurs temps</term>
<term>Foetus</term>
<term>Humains</term>
<term>Oxydoréduction</term>
<term>Relation dose-effet des médicaments</term>
<term>Régulation de l'expression des gènes</term>
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<front>
<div type="abstract" xml:lang="en">Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG) between cysteine residues and glutathione (GSH), can lead to cell death. Glutaredoxin 1 (Grx1) is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B), a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE) cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H₂O₂-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2), the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of
<i>Grx1</i>
by small interfering RNA (siRNA) significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H₂O₂-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage.</div>
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<AbstractText>Protein glutathionylation, defined as the formation of protein mixed disulfides (PSSG) between cysteine residues and glutathione (GSH), can lead to cell death. Glutaredoxin 1 (Grx1) is a thiol repair enzyme which catalyzes the reduction of PSSG. Therefore, Grx1 exerts strong anti-apoptotic effects by improving the redox state, especially in times of oxidative stress. However, there is currently no compound that is identified as a Grx1 activator. In this study, we identified and characterized Salvianolic acid B (Sal B), a natural compound, as a Grx1 inducer, which potently protected retinal pigment epithelial (RPE) cells from oxidative injury. Our results showed that treatment with Sal B protected primary human RPE cells from H₂O₂-induced cell damage. Interestingly, we found Sal B pretreatment upregulated Grx1 expression in RPE cells in a time- and dose-dependent manner. Furthermore, NF-E2-related factor 2 (Nrf2), the key transcription factor that regulates the expression of Grx1, was activated in Sal B treated RPE cells. Further investigation showed that knockdown of
<i>Grx1</i>
by small interfering RNA (siRNA) significantly reduced the protective effects of Sal B. We conclude that Sal B protects RPE cells against H₂O₂-induced cell injury through Grx1 induction by activating Nrf2 pathway, thus preventing lethal accumulation of PSSG and reversing oxidative damage.</AbstractText>
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